Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine

Haghikia A, Joerg S, Duscha A, Berg J, Manzel A, Waschbisch A, Hammer A, Lee DH, May C, Wilck N, Balogh A, Ostermann AI, Schebb NH, Akkad DA, Grohme DA, Kleinewietfeld M, Kempa S, Thoene J, Demir S, Mueller DN, Gold R, Linker R (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Immunity Elsevier

Book Volume: 43

Pages Range: 817-29

Journal Issue: 4

DOI: 10.1016/j.immuni.2015.09.007

Abstract

Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis.

Authors with CRIS profile

Anne Waschbisch Department of Neurology Ralf Linker Department of Neurology

Involved external institutions

Experimental and Clinical Research Center (ECRC) DE Germany (DE) Ruhr-Universität Bochum (RUB) DE Germany (DE) Stiftung Tierärztliche Hochschule Hannover (TiHo) DE Germany (DE) Technische Universität Dresden DE Germany (DE) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE)

How to cite

APA:

Haghikia, A., Joerg, S., Duscha, A., Berg, J., Manzel, A., Waschbisch, A.,... Linker, R. (2015). Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. Immunity, 43(4), 817-29. https://doi.org/10.1016/j.immuni.2015.09.007

MLA:

Haghikia, Aiden, et al. "Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine." Immunity 43.4 (2015): 817-29.

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